Alcoholic and non-alcoholic liver fibrosis remains an unsolved challenge for the hepatologist as it can lead to cirrhosis and end-stage liver disease, a life-threatening condition that necessitates liver transplantation. Current therapeutic strategies for the treatment of liver fibrosis include changes in diet, life-style and/or medications to alleviate the underlying cause of disease. Since liver disease is typically diagnosed following significant scar formation, adjuvant strategies that oppose the molecular and cellular program of fibrosis that drives liver disease and activate matrix degrading pathways are urgently required. A preponderance of preclinical data in models of fibrotic liver disease speaks to the beneficial effects of the naturally occurring peptide hormone Relaxin (H2R). Translation of these findings into clinical regimen has been painfully slow in large part due to the costs and logistical difficulties associated with commercial production of recombinant human H2R. To fully capitalize on the antifibrotic potential of H2R, Angion Biomedica Corp., NY and Chemical and Biopharmaceutical Laboratories (CBL, CO) have developed a library of H2R-like peptides in commercially viable quantities at a fraction of the cost associated with production of similar quantities of recombinant human H2R. Importantly, our preliminary studies suggest that these novel peptides share H2R-like bioactivity in vitro. The proposed SBIR Phase I program seeks to identify a lead antifibrotic candidate from within this library as a treatment for liver fibrosis. PUBLIC HEALTH RELEVANCE: Fibrotic liver disease is a major health and socioeconomic burden in the United States. Development of a clinically viable antifibrotic strategy against liver disease is of tremendous significance.